To evaluate the utility of human papillomavirus (HPV) DNA as molecular
marker for diagnostic screening of lymph nodes for cancer metastases,
we examined 16 involved and 124 histologically cancer-free nodes of 3
4 patients with cervical, vulval, or vaginal carcinomas associated wit
h HPV 6, 16, 18, 31, 33, 45, or X. All metastases of HPV-positive tumo
rs contained viral DNA of the same type as the primary cancer but in o
ne case the copy number of viral genomes was dramatically reduced. In
a varying proportion of histologically normal nodes of 7 of 23 patient
s with HPV 16-positive cancers HPV 16 DNA was revealed by Southern blo
t hybridization and/or PCR. Histologic reevaluation showed a metastasi
s in one case. Three examples of tumor heterogeneity regarding physica
l state or copy number of viral DNA are presented. Tumor heterogeneity
is discussed as possible explanation for apparently inconsistent resu
lts such as HPV-negative metastases of HPV-positive tumors.